Wilhelm Conrad Röntgen made the salient discovery of X-rays in 1985. In January 1986, only six months later, Emil Grubbé translated this discovery for the treatment of an advanced ulcerated breast cancer using a vacuum tube. Clinical radiotherapy has made significant technical advances since its early days of inception, growing into a technology driven tertiary specialty with significant contributions to curative and palliative treatments of cancer and health care cost. As a non-invasive approach of controlling gross tumor or the eradication of microscopic residual disease, it has been incorporated into the clinical management of most solid tumors.
Radiation therapy uses ionizing radiation to control or kill malignant cells. Radiation therapy may be curative in a number of types of cancer if they are localized to one area of the body. It may also be used as part of adjuvant therapy, to prevent tumor recurrence after surgery to remove a primary malignant tumor (for example, early stages of breast cancer). Ionizing radiation works by damaging the DNA of cancerous tissue leading to cellular death. To spare normal tissues (such as skin or organs which radiation must pass through to treat the tumor), shaped radiation beams are aimed from several angles of exposure to intersect at the tumor, providing a much larger absorbed dose there than in the surrounding, healthy tissue. Radiation may be used to provide palliative treatment where a cure is not possible and the aim is for local disease control or symptomatic relief, or as therapeutic treatment, where the therapy has survival benefit and it can be curative. Most common cancer types can be treated with radiation therapy. However, a major limitation to the appropriate application of this technology is the lack of any established means by which to identify patients with cancers that are more or less likely to respond to treatment.
Emerging advances in genomic technology have enabled a cataloguing of cancer genes that have resulted in the identification of genetic alterations that contribute to oncogenesis and/or tumor progression and in some cases have led to significant therapeutic advances in subsets of cancer patients. Druker et al., N Engl J Med 344, 1031 (Apr. 5, 2001); Rosell et al., Lancet Oncol 13, 239 (March, 2012). In contrast, radiotherapy regimens are delivered based on the site of anatomic origin of disease and do not currently take into account the genetic complexity that may regulate therapeutic response. Accordingly, there remains a need for a better understanding of what patients are more likely to benefit from radiation therapy, and the identification of additional agents that can be used together with radiotherapy to sensitize cancer cells to radiation.